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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003ECurrent management of gout is suboptimal, and patients often do not achieve serum uric acid (SUA) targets with allopurinol monotherapy. This article discusses the results of 2 replicate phase 3 studies known as Combining Lesinurad With Allopurinol in Inadequate Responders [CLEAR 1 and CLEAR 2; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01510158\u0026amp;atom=%2Fspmdc%2F14%2F51%2F10.atom\u0022\u003ENCT01510158\u003C\/a\u003E and \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01493531\u0026amp;atom=%2Fspmdc%2F14%2F51%2F10.atom\u0022\u003ENCT01493531\u003C\/a\u003E, respectively] conducted in symptomatic adults with gout.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disorders Rheumatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInflammatory Disorders\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ERheumatology Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EMore patients with gout who were randomized to the novel selective uric acid (UA) reabsorption inhibitor lesinurad in combination with allopurinol reached their serum uric acid (SUA) target compared with patients randomized to allopurinol plus placebo.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EKenneth G. Saag, MD, University of Alabama at Birmingham, Birmingham, Alabama, USA, reported the results of 2 replicate phase 3 studies known as Combining Lesinurad With Allopurinol in Inadequate Responders [CLEAR 1 and CLEAR 2; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01510158\u0026amp;atom=%2Fspmdc%2F14%2F51%2F10.atom\u0022\u003ENCT01510158\u003C\/a\u003E and \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01493531\u0026amp;atom=%2Fspmdc%2F14%2F51%2F10.atom\u0022\u003ENCT01493531\u003C\/a\u003E, respectively] conducted in symptomatic adults with gout. Current management of gout is suboptimal, and patients often do not achieve SUA targets with allopurinol monotherapy [Zhang W et al. \u003Cem\u003EAnn Rheum Dis.\u003C\/em\u003E 2006; Becker MA et al. \u003Cem\u003EN Engl J Med.\u003C\/em\u003E 2005]. Lesinurad inhibits the UA transporter 1, increasing UA excretion and thereby lowering SUA.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003ECLEAR 1 (US patients; n = 603) and CLEAR 2 (global study; n = 610) were 12-month multicenter, randomized, placebo-controlled studies in which lesinurad 200 and 400 mg QD, added to a medically appropriate stable dose of allopurinol (at least 300 mg QD, and at least 200 mg QD for those with moderate renal impairment), was compared with placebo plus allopurinol. Eligible patients had SUA levels \u2265 6.5 mg\/dL at the screening visit and \u2265 6.0 mg\/dL at the day 7 visit, and had \u2265 2 gout flares in the 12 months prior to randomization.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EIn both studies, patients were primarily white, and \u2265 90% were male. Mean ages were 51.9 years in CLEAR 1 and 51.2 years in CLEAR 2, and mean years since gout diagnosis were 11.84 and 11.53, respectively. Ninety-one percent of patients in CLEAR 1 and 84% in CLEAR 2 were receiving allopurinol 300 mg\/d at screening, and 14% and 23%, respectively, had tophi. Baseline SUA levels were 6.94 and 6.90 mg\/dL in CLEAR 1 and CLEAR 2, respectively.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EThe primary efficacy outcome\u2014the proportions of patients achieving their SUA target at 6 months\u2014was significantly greater for lesinurad 200 or 400 mg in combination with allopurinol compared with allopurinol alone in both CLEAR 1 and CLEAR 2 (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E).\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/10\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Percentage of Patients Achieving Serum Uric Acid \u0026amp;lt; 6.0 mg\/dL at Month 6a                \u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-709982268\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Percentage of Patients Achieving Serum Uric Acid \u0026amp;amp;lt; 6.0 mg\/dL at Month 6\u0026amp;lt;sup\u0026amp;gt;a\u0026amp;lt;\/sup\u0026amp;gt;                \u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/10\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/10\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/51\/10\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/15607\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EPercentage of Patients Achieving Serum Uric Acid \u0026lt; 6.0 mg\/dL at Month 6\u003Csup\u003Ea\u003C\/sup\u003E\n               \u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ERelative risks are post hoc calculations, not adjusted for randomization stratification factors.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EALLO, allopurinol; CLEAR, Combining Lesinurad With Allopurinol in Inadequate Responders; LESU, lesinurad; PBO, placebo; SUA, serum uric acid.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003E*\u003Cem\u003EP\u003C\/em\u003E \u0026lt; .0001 vs PBO + ALLO arm.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003E\n               \u003Csup\u003Ea\u003C\/sup\u003ENonresponder imputation. If a patient drops out or there are missing data, that patient is assumed to be a nonresponder, regardless of whether they were responding to treatment at the last measurement.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003EReproduced with permission from KG Saag, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EThe mean number of gout flares requiring treatment (end of month 6 through month 12) was not significantly different between treatment groups. The proportion of patients with complete tophus resolution by month 12 was also not significantly different between groups.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ELesinurad was generally well tolerated. At the 200-mg dose, the number of treatment-emergent adverse events was comparable between lesinurad plus allopurinol and placebo plus allopurinol. Serum creatinine increases \u2265 1.5 times were more common with lesinurad compared with placebo, with a high of 15.9% in CLEAR 1 patients treated with 400 mg of lesinurad in combination with allopurinol. The vast majority of cases of serum creatinine elevations resolved without interrupting study medication.\u003C\/p\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThere were few serious renal-related adverse events (AEs), with no difference in incidence between patients randomized to lesinurad 200 mg plus allopurinol and placebo plus allopurinol. The incidence of kidney stones was comparable between lesinurad 200 mg plus allopurinol and placebo plus allopurinol. The incidence of renal-related AEs and kidney stones was higher with lesinurad 400 mg plus allopurinol.\u003C\/p\u003E\n         \u003Cp id=\u0022p-11\u0022\u003ECombination therapy with lesinurad and allopurinol may represent a future treatment option for gout patients on allopurinol who warrant additional therapy, Dr Saag concluded.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/51\/10.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzodxe\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzodxe\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}